Chronic therapy with immunosuppressive drugs has been associated with an increased occurrence of neoplastic disease in certain clinical situations. Selected patients with systemic lupus erythematosus (SLE) and other inflammatory diseases of connective tissue are currently receiving therapy with cyclophosphamide, a potent suppressor of immune responsiveness. Clinical experience and therapeutic studies employing NZB/NZW mice have shown that cyclophosphamide therapy is associated with an increased incidence of neoplasms in the host with autoimmune disease. Many of these tumors were lymphomas. This information suggests that prolonged therapy of autoimmune disease with cyclophosphamide may predispose to the development of lymphoreticular tumors. Additional studies of Palmerston North mice in the laboratory of the principal investigator led to the discovery that these animals are models of SLE, comparable to New Zealand mice. Studies are underway to determine if cyclophosphamide is oncogenic in this strain of mice. The increased incidence of neoplastic lesions in cyclophosphamide-treated mice provided an opportunity to study lymphoma development in NZB/NZW mice. Some lymphomas suppressed ANA responses in terminal sera. Cells from those tumors have been implanted in recipient NZB/NZW mice, and it has been determined that their suppressive properties are sustained in recipient animals. BIBLIOGRAPHIC REFERENCES: Walker, S.E., and Bole, G.G., Jr.: Suppressed heterogeneous antinulcear antibody response in lymphoma-bearing NZB/NZW mice. Clin. Exp. Immunol. 24:210-217, 1976. Schecter, S.L., Bole, G.G., and Walker, S.E.: Midline granuloma and Wegener's granulomatosus - clinical and therapeutic considerations. J. Rheumatology 3:241-250, 1976.